Inflammaging as a Major Characteristic of Old People: Can It Be Prevented or Cured?
Department of Experimental Pathology and Interdepartmental Centre L. Galvani at the University of Bologna, Bologna, Italy.Nutrition Reviews (Impact Factor: 6.08). 12/2008; 65(12 Pt 2):S173-6. DOI: 10.1301/nr.2007.dec.S173-S176
Widespread aging at the population level is a recent phenomenon that emerged in affluent societies. Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name "inflammaging". Centenarians are unique in that, despite high levels of pro-inflammatory markers, they also exhibit anti-inflammatory markers that may delay disease onset. The key to successful aging and longevity is to decrease chronic inflammation without compromising an acute response when exposed to pathogens.
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- "The number of astrocytes, at least in human brains, for which the relevant counts were performed (Pelvig et al., 2008; Fabricius et al., 2013), does not change with age, remaining unaffected even in centenarians (Fabricius et al., 2013). Although the concept of the age-dependent increase in astroglial reactivity is quite widespread (Unger, 1998; Lynch et al., 2010) and is used to corroborate the ideas of the so called ''inflammaging'' (Franceschi, 2007), which regards brain senescence as a chronic neuroinflammation; the experimental data on this matter are, however, controversial. In aged animals a decrease (e.g. "
ABSTRACT: Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contribute to the ageing of the brain and to neurodegenerative diseases. Changes in astroglia in ageing and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter homeostatic reserve of the brain and contribute to early cognitive deficits. At the later stages of AD reactive astrocytes are associated with neurite plaques, the future commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortex astrocytes to not mount gliotic response to emerging β-amyloid deposits. This deficits in reactivity coincides with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at prevention and cure of neurodegenerative disorders. Copyright © 2015. Published by Elsevier Ltd.
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- "These systemic toxicities were closely representative of those previously noted clinically with FDAapproved immu nostimulatory IT therapeutics such as highdose IL2 and IFN (Lee and Margolin, 2011). Aging is associated with a gradual decline in immunolog ical function but is also accompanied by the coincidence of a systemic, chronic, and lowgrade proinflammatory response termed inflammaging that leads to increased systemic cyto kine levels, namely IL1, IL6, and TNF (Franceschi, 2007). "
ABSTRACT: Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF(+) macrophages in response to αCD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with αCD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon αCD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT.
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- "Lymphocyte re-population and their differential and activation abilities are altered due to a decreased volume of hematopoietic bone marrow tissue, reduced progenitor potential, and thymus involution (Sharma et al., 2009;Qi et al., 2014). The basal level and injury-triggered production of proinflammatory cytokines are increased in the elderly, which is indicative of persistent low-grade inflammatory processes (Franceschi, 2007). Hence, immunosenescence affects the integrated ability to respond appropriately to immediate neurological injury and results in decrements in the ability of tissues to regain homeostasis. "
ABSTRACT: Non-invasive criteria determining the progress of brain healing are especially important in aging, providing a case-specific therapeutic strategy in population with dysregulated neurorepair mechanisms. We hypothesized that temporal evolution of magnetic resonance imaging (MRI) of T2 tissue relaxation values correlate with neurological severity scores (NS), and provide a robust indicator of aging brain healing after stroke. Pre-treatment of aged rats with brain-only proton irradiation was undertaken to pre-condition the inflammatory system. Irradiation was performed 10 days prior to right middle cerebral artery occlusion (MCAO) for 50 min (MCAO+Rad). Control rats included naïve (no ischemia, no radiation), irradiated-only (Rad), irradiated ischemic, or ischemic-only (MCAO). MRI of the temporal lobe and NS were obtained at 3, 14 and 28 days post-stroke. At 28 days post-stroke, immunofluorescence for visualizing blood vessels (Von Willeband factor; vWF), neurons (neuronal nuclear antigen; NeuN), astrocytes (glial fibrillary acidic protein; GFAP), activated microglia/macrophages (ionized calcium-binding adapter molecule 1, Iba1), T-lymphocytes (CD3), phagocytes (ED1) and apoptotic cells (caspase-3) were assessed. We found a positive T2-NS correlation in irradiated, ischemic rats that corresponded to late-stage brain recovery. Late-stage brain recovery was characterized by improved neovascularization, formation of glio-vascular complexes (visualized by GFAP/vWF) and enhanced neuronal viability (by NeuN/Caspase3) in the peri-lesional zone. The immune response plateaued at the late stage of repair as evidenced by significantly decreased expression (41.7%) and distribution of phagocytes (phagocytic rim decreased 44.6%). We also found reduced infiltration of T-lymphocytes (CD3) in brain and normalization of blood lymphocytes. The observed T2-NS correlations may provide a simple MRI-based criterion for recognition of regenerative brain transformation in aged patients following stroke. Selective activation of innate immunity and accelerated transition from pro-inflammatory to pro-healing macrophage phenotypes induced by localized brain irradiation is a potential mechanism for enhancing repair ability in the elderly.